Table 1.
Summary of trial characteristics
| Drug | No of studies | No of patients | Year published, median (range) | Early escape design, % of studies (No of patients) | Trial duration*, median (range) weeks | MTX dose >15 mg/wk†, % of studies (No of patients) | Disease duration, median (range) years | Swollen joint count, median (range) |
|---|---|---|---|---|---|---|---|---|
| MTX + bDMARDs/tofacitinib: | ||||||||
| MTX + etanercept | 10 | 2448 | 2007 (1999-2014) | 0 | 38 (12-52) | 50 (n=1833) | 2 (0.5-13) | 13.9 (11-24) |
| MTX + infliximab | 13 | 2806 | 2006 (2000-14) | 8 (n=264) | 26 (13-54) | 46 (n=1990) | 7.6 (0.4-10.5) | 15 (5-21.5) |
| MTX +adalimumab | 16 | 4465 | 2010 (2003-15) | 38 (n=1936) | 24 (12-104) | 50 (n=1809) | 2.5 (0.1-11.7) | 16.3 (8.7-22.5) |
| MTX + rituximab | 4 | 1262 | 2008 (2004-12) | 25 (n=342) | 24 (24-104) | 50 (n=683) | 8.6 (0.9-11.5) | 20.9 (20.2-21.6) |
| MTX + abatacept | 10 | 3612 | 2012 (2005-15) | 0 | 25 (17-52) | 60 (n=3014) | 6.4 (0.5-9.3) | 17.1 (10-22.4) |
| MTX + tocilizumab | 10 | 4859 | 2012 (2006-16) | 50 (n=3671) | 24 (16-52) | 60 (n=2729) | 6.6 (0.4-9.2) | 13.7 (6.4-20.1) |
| MTX + certolizumab | 7 | 2680 | 2012 (2008-15) | 71 (n=1561) | 24 (24-52) | 29 (n=1119) | 6 (0.3-9.6) | 21 (16.4-22.5) |
| MTX + golimumab | 6 | 1640 | 2012 (2008-13) | 83 (n=1570) | 24 (16-52) | 50 (n=1132) | 6.9 (3.2-8.7) | 13.5 (11.6-15.4) |
| MTX + tofacitinib | 4 | 749 | 2012 (2011-15) | 50 (n=621) | 24 (12-52) | 50 (n=621) | 8.7 (0.7-9.1) | 14.7 (14.1-14.9) |
| Subtotal | 80 | 24 521 | 2011 (1999-2016) | 31 (n=9965) | 24 (12-104) | 50 (n=14930) | 6.3 (0.1-13) | 16.4 (5-24) |
| Comparative effectiveness trials: | ||||||||
| Head-to-head bDMARDs/tofacitinib | 4 | 1658 | 2010 (2006-14) | 25 (n=501) | 27 (26-104) | 50 (n=1077) | 7.8 (1.8-11.3) | 16.6 (15.9-20.6) |
| MTX + bDMARDs v MTX + csDMARDs | 4 | 1382 | 2012 (2012-13) | 0 | 63 (16-104) | 25 (n=353) | 0.5 (0.3-5.2) | 12 (11.2-12.8) |
| Subtotal | 8 | 3040 | 2012 (2006-14) | 12 (n=501) | 27 (16-104) | 38 (n=1430) | 5.2 (0.3-11.3) | 15.9 (11.2-20.6) |
| MTX + csDMARDs: | ||||||||
| MTX + azathioprine | 1 | 209 | 1992 | 0 | 24 | 0 | 8.6 | 17.3 |
| MTX + hydroxychloroquine/ chloroquine | 7 | 452 | 2005 (1993-2012) | 0 | 26 (12-52) | 0 | 4 (0.3-7.7) | 10.7 (8.2-27.3) |
| MTX + sulfasalazine | 6 | 639 | 2000 (1994-2007) | 0 | 52 (24-76) | 0 | 0.4 (0.2-5) | 16.7 (9.8-22.6) |
| MTX + ciclosporin | 9 | 1100 | 2003 (1995-2008) | 11 (n=120) | 48 (16-104) | 22 (n=64) | 1.1 (0.2-10.3) | 13.6 (11-19) |
| MTX + sulfasalazine + hydroxychloroquine | 4 | 503 | 2005 (1996-2013) | 0 | 91 (13-104) | 0 | 4.4 (0.5-8.6) | 17.1 (9.5-29.8) |
| MTX + leflunomide | 3 | 921 | 2006 (2002-15) | 0 | 24 (16-36) | 67 (n=455) | 6.2 (0.7-11.6) | 14.3 (10.7-18) |
| MTX + IM gold | 1 | 65 | 2005 | 0 | 48 | 100 (n=65) | 3.2 | 11 |
| Subtotal | 31 | 3889 | 2003 (1992-2015) | 3 (n=120) | 48 (12-104) | 16 (n=584) | 1.1 (0.2-11.6) | 13.6 (8.2-29.8) |
| MTX v csDMARD monotherapy: | ||||||||
| Placebo | 5 | 324 | 1985 (1985-93) | 20 (n=52) | 14 (12-18) | 0 | 9.5 (4.8-14) | 27.5 (24-30.9) |
| Azathioprine | 5 | 257 | 1991 (1987-94) | 0 | 24 (24-52) | 0 | 12 (8.7-13.9) | 14.6 (9.5-21.9) |
| IM gold | 5 | 489 | 1991 (1988-2001) | 0 | 48 (26-52) | 20 (n=99) | 4 (1.2-6) | 14 (13.9-15.2) |
| Sulfasalazine | 2 | 211 | 1998 (1995-2002) | 0 | 24 | 0 | 4 (1.4-6.6) | 9.3 |
| Ciclosporin | 2 | 203 | 1999 (1998-2000) | 0 | 65 (26-104) | 50 (n=100) | 3.8 (2.2-5.5) | 13.1 (12.2-14) |
| Leflunomide | 16 | 3258 | 2002 (1999-2014) | 12 (n=567) | 24 (12-52) | 25 (n=927) | 3.9 (0.5-6.8) | 11.8 (8.2-16.5) |
| Hydroxychloroquine | 2 | 409 | 2006 (2000-12) | 0 | 24 | 0 | 1.5 (1-2.1) | NA |
| SC v oral MTX | 2 | 467 | 2009 (2008-10) | 50 (n=383) | 24 | 100 (n=467) | 0.2 | 15 |
| Subtotal | 39 | 5618 | 2000 (1985-2014) | 10 (n=1002) | 24 (12-104) | 21 (n=1593) | 4.5 (0.2-14) | 14 (8.2-30.9) |
| Total | 158 | 37 068 | 2008 (1985-2016) | 20 (n=11 588) | 24 (12-104) | 35 (n=18537) | 4.8 (0.1-14) | 15.1 (5-30.9) |
Trials are grouped by comparator and sorted by year of first trial within each class, for illustrative purposes. Patients’ characteristics, including number of patients, include only arms considered in review.
DMARD=disease modifying antirheumatic drug; bDMARD; biologic DMARD; csDMARD=conventional synthetic DMARD; tsDMARD=targeted synthetic DMARD; IM=intramuscular; MTX=methotrexate; SC=subcutaneous; SJC=swollen joint count.
*Trial duration for efficacy outcomes; some studies had longer follow-up for safety outcomes.
†Studies for which dose of methotrexate could be confirmed as ≥15 mg/week; in some studies, methotrexate was dosed across a range of values that included 15 mg/week, but the actual dose was not provided.